Abstract
Current literature confirms presence of endothelial cell dysfunction in diabetes compared to non-diabetes state. However there is lack of data on endothelial function in Pre-diabetes (defined as per Diabetes Care, Clinical Guideline, Jan'11 ). Methods: We selected exercise-naive patients, 20-70 yrs, BMI 25-34.9, n=20 in each group and studied their endothelial function after 150min/week of aerobic exercise (similar to Diabetes Prevention Program) and after non exercise phase (6wks phase each), in a cross over design with a 4 wk wash-out period between the 2 groups. For endothelial function assessment we looked at, 1. flow mediated dilatation (FMD of brachial artery), 2. CD34/KDR +ve cell count from peripheral blood derived mononuclear cell fraction at day0 by Flow cytometry (FACS) 3. endothelial progenitor cell (EPC) associated colony-forming units (Hill-CFU) at day5 of culture, 4.endothelial bio-inflammatory markers and BP, fasting lipids, insulin, glucose. We also looked at gene expression profile of critical endothelial function genes in CD34/KDR+ve cells. Results: FMD studies (undertaken by 3 observers, blinded to glycemic status) showed, mean FMD in non-exercise group of 5.7+0.6% and post exercise it improved to 11.2±0.9%. Both CFU estimation, at day5 and CD34/KDR +ve cells estimation at day0 showed significant increase in numbers following exercise. There was no weight loss noted between 2 groups, however, there was statistically significant reduction in leptin, IL-6, TNFα, fasting Triglyceride, LDL and ApoB levels. Insulin sensitivity (HOMA) improved in the exercise group. Gene expression analysis of CD34+ve cells showed decrease of eNOS and increase of PECAM-1 in non-exercise which improved significantly following exercise, with no change in von-Willebrand's factor. Summary: Prediabetic patients have significant endothelial dysfunction, similar to patients with diabetes. In this population, FMD measurements and CD34/KDR+ve cell number and gene profile assays along with usual biochemical markers can serve as robust bio-markers for monitoring endothelial cell dysfunction. Conclusion: Pre-diabetic state is associated with significant endothelial dysfunction which can be improved, by undertaking regular aerobic exercise.
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